The inhibitory action of tea (Camellia sinensis) and tea components against carcinogensis has been demonstrated in several animal models. It is not clear, however, whether tea comsumption prevents cancer in humans. Our research goal is to bridge this gap of knowledge by studing the biological fate of tea polyphenols (the putative active components), the pertinent cancer inhibitory mechanisms, and the dose response relationships of the inhibition using the knowledge gained and the analytical methods developed in the previous grant period. The specific aims are as follows: (1.) To understand the biological fate of key tea components by studying the plasma, salivary, and urinary levels of tea polyphenols in human volunteers after ingestion of tea at different dose regimens. This information is essential for understanding the biological effects of tea in humans. (2.) To characterize the inhibitory actions to tea in the 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogensis model with A/J mice by studying the temporal and dose- response relationships for the inhibition. The relationship between the quantity of tea consumed and tissue/plasma levels of tea polyphenols will be established. Mechanistic information will be obtained by correlating anti-proliferative and anti-tumorigenic activities as well as their relationship to tissue levels of tea polyphenols. (3.) To evaluate the importance of (-)-epigallocatechin, (-)- epigallocatechin gallate, theaflavins, and other tea components in the inhibition of carcinogenesis and to elucidate the molecular mechanisms involved. Specific Aim 1 will determine the plasma levels of tea polyphenols in humans due to specific dose regimens of tea consumption. Specific Aims 2 and 3 will determine the relationship between plasma/tissue levels to tea polyphenols and the inhibition of tumorigenesis. Together, these results will provide the basis for a quantitative assessment of the effects of tea consumption of human cancers in epidemiological studies and for designing cancer prevention trials.